P63 BREAKTHROUGH COVID-19 IN FULL VACCINATED PATIENTS WITH MULTIPLE MYELOMA: A SINGLE CENTER EXPERIENCE OF 54 PATIENTS
Authors: N. Sgherza, P. Curci, R. Rizzi, A. Perfetto, O. Battisti, N. Pizzileo, G. De Trizio, P. Musto
Journal: HemaSphere (2023)

COVID-19-related mortality in the onco-hematological setting is higher than in general population and patients with multiple myeloma (MM) are reported to be particularly vulnerable to SARS-CoV-2 infection, due to compromised humoral and cellular immunity (related to disease itself) and to anti-tumor treatments. Thus, along with general measures, vaccines against SARS-CoV-2 have become, from their approval, the most important strategy to prevent poor outcome from COVID-19 in MM patients. However, limited data have been so far published about epidemiology and outcome of breakthrough COVID-19 in MM patients after three anti-SARS-CoV-2 vaccine doses. We performed a retrospective analysis of 54 consecutive patients with active MM who experienced SARS-CoV-2 infection between December, 2021, and December, 2022 at our Institution (Table 1). Among them, four cases of “reinfection” were documented. All patients had received three doses of anti-SARS-CoV2 vaccines (mostly mRNA) and 6 of them had also received a fourth, “second booster” dose. SARS-CoV-2 infections were diagnosed by RT-PCR or by antigen rapid test on nasopharyngeal swabs. Data about sex, age, ongoing treatment, symptoms, hospitalization, mortality, and additional use of antiviral drugs or monoclonal antibodies for the treatment of COVID-19 were collected. The median age of the whole group was 65 years (IQR: 60-76; range: 39-84), with male preponderance (59.3%). Half of the patients (27) had at least one underlying comorbidity, with chronic cardiopathy (i.e., hypertension, atrial fibrillation) being the most reported. The most frequent isotype was IgG, followed by IgA, light chain and non-secreting subtype. Median number of days between the last dose of vaccine and infection was 136.5 (IQR: 89-199.2; range: 11-381). About disease status at SARS-CoV-2 breakthrough infection, 27 cases (50%) were newly diagnosed/first line MM, 20 (37%) were first relapses, 7 (13%) were further relapsed MM. Forty-eight patients (88.9%) were under treatments including dexamethasone (64.8%), proteosome inhibitors (25.9%), IMiDs (75.9%), anti-CD38 monoclonal antibodies (44.4%) or other therapies (7.4%). Six patients (11.1%) in complete response, three of whom after autologous transplantation and one after CAR-T treatment, were in follow-up, without active therapy. Infection was symptomatic in 35 patients (64.8%) and the most common symptoms were fever, cough, sore throat and runny nose. Overall, 4 patients (7.4%) were hospitalized: among them, 1 (1.8%) was admitted to an intensive care unit (ICU) due to respiratory distress. Fourteen patients (25.9%) received specific anti-SARS-CoV-2 treatment: 7molnupivar, 5 PF-07321332/ritonavir, 1 PF-07321332/ritonavir + sotrovimab, 1 sotrovimab. After a median follow-up of 258 days (IQR: 181-294; range: 43-356), 3 patients (5.6%) had died and no patient reported long-lasting symptoms. Our data indicate that SARS-CoV-2 infection remains frequent even in “triple vaccinated” MM patients, but also that the clinical outcome of COVID-19 appears to be significantly improved by a “booster” dose of vaccine with respect to pre-vaccination era in this high risk population exposed to novel Omicron variants. The role of new antiviral agents and monoclonal antibodies, currently used to reduce the risk of progression of COVID-19 to severe disease, warrants to be further investigated in larger series. Table 1 - Characteristics of 54 full vaccinated MM patients with SARS-CoV-2 infection Age, years Median (IQR)Range 65 (60-76)39-84 Sex, n. (%)MaleFemale 32 (59.3)22 (40.7) Comorbidities, n. (%)012≥3 27 (50)16 (29.7)5 (9.2)6 (11.1) MM subtype, n. (%)IgGIgALight chainNon-secreting 33 (61.1)12 (22.2)7 (13)2 (3.7) Days from last vaccine dose to SARS-CoV-2 infection Median (IQR)Range 136.5 (89-199.2)11-381 Disease status, n. (%)Newly diagnosed/First line1st RelapseRelapse-Refractory 27 (50)20 (37)7 (13) Current MM treatment, n. (%) Dexamethasone Contains Proteosome inhibitor Bortezomib Carfilzomib Ixazomib Contains IMiD (including maintenance therapy) Thalidomide Lenalidomide Pomalidomide Contains CD38 mAb Daratumumab Isatuximab Contains other Elotuzumab, Belantamab Mafodotin Melphalan No therapies 48 (88.9)35 (64.8)14 (25.9)93241 (75.9)632324 (44.4)2224 (7.4)211 6 (11.1) COVID-19 outcome, n. (%)Presence of symptomsHospitalizationHospitalization in ICUDeath to COVID-19 35 (64.8)4 (7.4)1 (1.8)3 (5.6) COVID-19 symptoms, n. (%)FeverCoughSore throatRunny noseFatigueDiarrhea 28 (80)14 (40)11 (31.4)11 (31.4)6 (11.1)3 (8.6) Treatment, n. (%)MolnupiravirPF-07321332/RitonavirPF-07321332/Ritonavir + SotrovimabSotrovimabNone 7 (13)5 (9.3)1 (1.8)1 (1.8)40 (74.1)